Photodynamic therapy with local photosensitizer delivery inhibits experimental intimal hyperplasia

Adili, Farzin; Eps, Randolph G. Statius van; Flotte, Thomas J.; LaMuraglia, Glenn M.

doi:10.1002/(sici)1096-9101(1998)23:5<263::aid-lsm6>3.0.co;2-v

Cited by 22 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During 48 hours, patients are photosensitive and advised not to come in contact with direct bright (sun)light and to cover themselves with sunglasses and clothes 13 . In animal studies, mild extravascular hemolysis and hematopoiesis were noted in inactivated daily doses 32–70 times (in dogs and rats) as high as advised in humans when administered for 4 weeks 14 . Fast admission of 2.0 mg/kg in pigs under general anesthesia led to hemodynamic instability and diphenhydramine decreased these effects, suggesting histamine-related processes.…”

Section: Discussionmentioning

confidence: 97%

Verteporfin as a Medical Treatment in Peyronie’s Disease

et al. 2018

View full text Add to dashboard Cite

IntroductionIn Europe and the United States, verteporfin (Visudyne; VP) is registered and used in treating macular degeneration. Research showed that VP decreased expression of fibrotic genes in fibroblasts collected from nodules of patients suffering from Dupuytren’s disease, plausibly by de-activating transcription in the Yes Activated Protein (YAP) pathway.AimTo analyze the effect of VP on myofibroblasts cultured from Peyronie’s disease (PD) plaques.MethodsAt surgery for PD we took biopsies from the plaques of 5 patients. By immunostaining, the presence of the pathologic myofibroblasts was determined. After culturing cells, VP was dispensed in starvation medium for 24 and 48 hours and messenger(m)RNA levels of COL1A1, ACTA2, COL5A1, EDA-FN, LOXL2, CCN2, SERPINH1, PLOD2, and YAP were quantified and compared with controls with real-time polymerase chain reaction.Main Outcome MeasuremRNA-levels of COL1A1, ACTA2, COL5A1, EDA-FN, LOXL2, CCN2, SERPINH1, PLOD2, and YAP.ResultsThe pathologic phenotype of cells isolated from PD plaques was confirmed with baseline immunofluorescent stainings that showed considerable levels of α-smooth muscle actin, being a marker for the presence of myofibroblasts. The mRNA ratios of all the genes related to fibrosis (COL1A1, etc.) except YAP decreased significantly after treatment with VP within 24 and 48 hours. These results suggest inhibition of fibrosis in the YAP cascade, downstream of YAP.ConclusionIn our opinion, urologists must move the focus to disease before deformity, and the search for new oral or intralesional agents, well-tolerated and effective in both the acute and chronic phase of PD must continue. VP blocked the expression of genes related to fibrosis in the YAP cascade in myofibroblasts derived from PD plaque.Mohede DCJ, de Jong IJ, Bank RA, et al. Verteporfin as a medical treatment in Peyronie’s disease. Sex Med 2018;6:302–308.

show abstract

Section: Discussionmentioning

confidence: 97%

Verteporfin as a Medical Treatment in Peyronie’s Disease

et al. 2018

View full text Add to dashboard Cite

show abstract

“…[2][3][4][5] In vivo studies have shown that PDT represents a safe, effective method of inhibiting the development of intimal hyperplasia. 6,7 Furthermore, a PDT-mediated reduction in the number of smooth muscle cells (SMCs) occurs along with the prevention of the inflammatory infiltration, aneurysmal dilatation, and development of intimal hyperplasia associated with allograft rejection. 8 Although recent studies have suggested that PDT-induced apoptosis plays a primary role in the reduction of intimal hyperplasia in ballooninjured rat carotid arteries, 9 little is known regarding the biochemical effects of PDT on SMCs.…”

mentioning

confidence: 99%

Mitochondrial Release of Apoptosis-Inducing Factor and Cytochrome c During Smooth Muscle Cell Apoptosis

Granville

Cassidy

Ruehlmann

et al. 2001

The American Journal of Pathology

View full text Add to dashboard Cite

Photodynamic therapy (PDT) is under investigation for the treatment of intimal hyperplastia in conditions such as atherosclerosis and restenosis. Although smooth muscle cells (SMCs) may be a key target for treatment, the effects of PDT on these cells are poorly characterized. In the present study, apoptosis was induced in primary human aortic SMCs by the combination of the photosensitizer verteporfin and visible light. After PDT, an increase in mitochondrial cytochrome c (cyt c) and apoptosis-inducing factor (AIF) levels were detected in the cytosol immediately and their levels increased steadily up to 2 hours. Cytosolic levels of the pro-apoptotic Bcl-2 family member Bax decreased reciprocally throughout this period, but this change did not occur before cyt c release. Confocal microscopy revealed a diffuse staining pattern of cyt c within apoptotic cells as compared to a distinct mitochondrial staining in normal cells. AIF translocated from mitochondria to the nucleus during the progression of apoptosis. After cyt c release, caspase-9 and caspase-3 processing was visible by 1 hour and caspase-6, -7, and -8 processing was apparent by 2 hours after PDT. In summary, these results demonstrate for the first time the cellular redistribution of mitochondrial AIF during SMC apoptosis, as well as the early release of cyt c and the subsequent activation of multiple caspases during PDT-induced SMC apoptosis. Photodynamic therapy (PDT) is a clinically approved treatment for various types of cancer and the ocular condition known as age-related macular degeneration, the leading cause of blindness in the elderly. PDT is also under investigation for the treatment of other ocular disorders as well as atherosclerosis, restenosis, allograft rejection, and autoimmune disorders. 1 PDT catalyzes the formation of reactive oxygen intermediates and rapidly induces apoptosis in a variety of cell types after light irradiation. [2][3][4][5]

show abstract

“…12,27,28 In addition, the basic principle of local delivery in the rat model by means of direct intraluminal pressure to deliver the photosensitizer to a vessel segment has been investigated with the lipo-somal dye benzoporphyrin-derivative. 29 The ability of vascular PDT to inhibit IH in the rodent model was also confirmed in large animal models. 30,31 However, because of dosimetry issues, these were short-term experiments, and the development of IH was not completely inhibited.…”

Section: B a Discussionmentioning

confidence: 85%

Local photodynamic action of methylene blue favorably modulates the postinterventional vascular wound healing response

Heckenkamp

Adili

Kishimoto

et al. 2000

Journal of Vascular Surgery

Self Cite

View full text Add to dashboard Cite

Photodynamic therapy (PDT), the light activation of photosensitizers to produce free radicals, is known to inhibit experimental intimal hyperplasia (IH). However, its clinical application has been limited by the lack of a suitable approach and a clinically appropriate photosensitizer. The aim of this study was to determine the effectiveness of a clinical approach for PDT, while testing its ability to favorably modulate the vascular wound healing response. Methods: Rat carotid arteries were balloon-injured (BI), and for PDT, the arteries were irradiated with thermoneutral laser light (λ = 660 nm, 100 J/cm 2 ) after the photosensitizer methylene blue (MB) was delivered locally. Control rats included BI alone and MB after BI alone. Arteries were analyzed after 2 weeks with morphometric evaluation (n = 6) and in situ hybridization for versican and procollagen type I gene expression (digitized image pixel analyses, n = 3). Results: No IH developed in PDT-treated arteries (0 ± 0 mm 2 ; compared with BI, 0.192 ± 0.006 mm 2 ; P < .0001). The diameters remained unchanged (PDT, 0.95 ± 0.04 mm; BI, 0.94 ± 0.05 mm; uninjured artery, 0.91 ± 0.06 mm). Arterial injury resulted in an increase of versican and procollagen type I messenger RNA (mRNA) in the adventitia and neointima. In the repopulating cells of the adventitia after PDT, there was a significant decrease in versican mRNA (% of positive pixels per high-power field: PDT, 1.13% ± 0.39%; BI, 2.93% ± 0.61%; P < .02), but not in procollagen type I mRNA. Conclusion:The decrease of versican mRNA expression of repopulating cells after PDT reflects favorable healing on a molecular level. Site-specific delivery of MB, a clinically appropriate photosensitizer, followed by PDT represents a suitable method to promote favorable healing after balloon intervention and further supports its role for inhibiting postinterventional restenosis.

show abstract

Photodynamic therapy with local photosensitizer delivery inhibits experimental intimal hyperplasia

Cited by 22 publications

References 27 publications

Verteporfin as a Medical Treatment in Peyronie’s Disease

Verteporfin as a Medical Treatment in Peyronie’s Disease

Mitochondrial Release of Apoptosis-Inducing Factor and Cytochrome c During Smooth Muscle Cell Apoptosis

Local photodynamic action of methylene blue favorably modulates the postinterventional vascular wound healing response

Contact Info

Product

Resources

About